The first major objective of this research is to purify the enzymes of the glycogen synthase system from the cortex and medulla of the kidney: 1), 2) Synthase D 3) Synthase D phosphatase, and 4) Synthase I kinase. It will be established if synthase I kinase is identical to the cyclic AMP dependent protein kinase. The second major objective is to characterize the physical and kinetic properties of the four enzymes of the renal glycogen synthase system. Those properties of the enzyme which may be important in the regulation of renal glycogen synthesis will be emphasized. The third major objective is to establish how the renal glycogen synthase system is regulated. Using the renal cortex (slowly metaboli zes glycogen) and medulla (rapidly metabolizes glycogen) as model, I will try to establish if glycogen synthase is regulated by an interconversion of synthase, direct metabolite control of synthase activity, or a combination of both mechanisms. Experiments will be performed on tissue slices from cortex and medulla. An attempt will be made to correlate the rate of glycogen synthesis with the levels of the enzymes of the glycogen synthase system, with the concentration of substrates (glycogen and UDPGIc), and with the concentration of effectors of the glycogen synthase system. In addition to the above goals related directly to the kidney, a general goal is to contribute to an understanding of the regulation of mammalian glycogen metabolism. As progress is made in the kidney study, new concepts which come out of this work will be applied to other tissues (i.e. liver and skeletal muscle).